2001 Fiscal Year Final Research Report Summary
Analysis of the immune response of tumor-bearing host at the immunochemotherapy -from the viewpoint of optimum combination of chemotherapy and immunotherapy -
| Project/Area Number |
12671212
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Kanazawa University |
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Principal Investigator |
FUJIMOTO Toshihiro Kanazawa University, Medical School, Assistant Professor, 医学部・附属病院, 講師 (00242561)
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| Co-Investigator(Kenkyū-buntansha) |
MAI Masayoshi Kanazawa University, Cancer Research Institute, Professor, がん研究所, 教授 (80092807)
TAKAHASHI Yutaka Kanazawa University, Cancer Research Institute, Associate Professor, がん研究所, 助教授 (10179541)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Irinotecan(CPT-11) / OK-432 / Th1 / IL-12 / immunochemotherapy / tumor bearing state |
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| Research Abstract |
Chemotherapy with lower dose of irinotecan (CPT-ll) exerts larger antitumor effect. In this study, SN-38, the active metabolite of CPT-ll, exerted dose-dependent inhibition of interferon (IFN)-γ and interleukin (IL)-10 production induced by streptococcal preparation OK-432 in mouse splenocytes. In contrast, the optimum concentration of SN-38 (0.4-0.8(μg/ml) increased IL-6 and IL-12 production by OK-432 activated macrophages. In tumor-bearing mice (C57BL/6 mice bearing with B16 melanoma), CPT-11 inhibited tumor growth and OK-432 had an additive antitumor effect with CPT-11. Investigation of cytokine production showed that CPT-11 treatment principally inhibited IL-12 and IFN-γ production, which was improved by the combined administration with OK-432. These results indicate that CPT-11 inhibits type-1 T helper (Th1) cells despite its potential to stimulate macrophages and that OK-432 enhances the antitumor activity of CPT-11 by increasing Th1-cytokine production (Anticancer Research 21 : 2505-2510, 2001).
In the treatment for the peritoneal metastasis of gastric carcinoma, we may control disseminated cancer cells by intraperitoneal immunochemotherapy using MMC and OK432 in patients with curative resection (Oncology, 2002, in press).
Briefly, these results have demonstrated the efficacy of the combination of chemotherapy and immunotherapy.
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